PXD067316 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma |
| Description | Many safe and effective drugs have unknown targets, limiting opportunities to extend their use to other disease states with overlapping etiologies. Here, we have elucidated the mechanism of action of the direct vasodilator, hydralazine (HYZ), which has been used for more than seven decades and remains on the World Health Organization's List of Essential Medicines as a treatment for preeclampsia and hypertensive crisis. Using our chemoproteomic drug de-orphanization approach, we identify a key enzyme mediator of targeted protein degradation, 2-aminoethanethiol dioxygenase (ADO), as a selective HYZ target. The structure of the ADO•HYZ complex shows that the drug chelates the enzyme's metal cofactor in the course of alkylating one of its ligands. The resultant inactivation stabilizes regulators of G-protein signaling (RGS4/5) that are normally marked for degradation by ADO. This activity explains the drug's impact on blood vessel tension, and it comports with prior associations of insufficient RGS levels with both clinical preeclampsia and analogous symptoms in mice. The established importance of ADO in glioblastoma motivated evaluation of the efficacy of HYZ against such cells, revealing that a single dose induces prolonged senescence. The results identify ADO as a novel pharmacological target for both diseases and connect it to a known drug, opening avenues for the rational tailoring of HYZ to create new pharmaceuticals. |
| HostingRepository | PRIDE |
| AnnounceDate | 2025-10-24 |
| AnnouncementXML | Submission_2025-10-24_00:04:37.438.xml |
| DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD067316 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Kyosuke Shishikura |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Fusion |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-08-13 13:03:11 | ID requested | |
| ⏵ 1 | 2025-10-24 00:04:38 | announced | |
Publication List
Keyword List
| submitter keyword: glioblastoma, hydralazine,LC-MS, preeclampsia, mechanisms of action |
Contact List
| Megan L. Matthews |
|---|
| contact affiliation | Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA |
| contact email | megamatt@sas.upenn.edu |
| lab head | |
| Kyosuke Shishikura |
|---|
| contact affiliation | University of Pennsylvania |
| contact email | kyosuke@sas.upenn.edu |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD067316 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD067316
- Label: PRIDE project
- Name: Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma
